Glucokinase gene polymorphisms: a genetic marker for glucose intolerance in a cohort of elderly Finnish men.
McCarthy MI., Hitman GA., Hitchins M., Riikonen A., Stengård J., Nissinen A., Tuomilehto-Wolf E., Tuomilehto J.
Although mutations in the glucokinase gene are implicated in the pathogenesis of glucose intolerance in pedigrees with maturity-onset diabetes of the young, the role of such mutations in typical Type 2 diabetes is poorly characterized. We studied a cohort of elderly men born (between 1900 and 1919) in two Finnish communities and exhibiting a continuous spectrum of glucose tolerance at assessments made in 1984 and 1989. Individuals were typed at two polymorphic microsatellites straddling the glucokinase gene, GCK(3') (n = 169) and GCK(5') (n = 166): these two markers were in linkage equilibrium in this cohort. Significant associations between alleles at the GCK(3') marker and glucose tolerance were evident (p = 0.002), the frequency of the (z + 2) allele rising from zero in control subjects (n = 88 chromosomes) to 6.5% (n = 62) in subjects with impaired tolerance and 12.2% (n = 188) in subjects with diabetes. Mean 2-h glucose levels were 10.5 (9.6-11.4, 95% confidence interval) mmol l-1 in individuals with the (z + 2) allele and 8.1 (7.6-8.7) mmol l-1 in those without (p = 0.01, corrected for multiple comparisons). No association was evident between GCK(5') alleles and glucose tolerance. The GCK(3') microsatellite is a marker for abnormal glucose tolerance in this cohort of elderly Finnish men.